Background. Treatment of freezing of gait (FOG) is always challenging because of its unpredictable nature and multifactorial physiopathology. Intestinal levodopa infusion has been proposed in recent ...years as a valuable option for its improvement. FOG in Parkinson’s disease (PD) can appear after deep brain stimulation in patients who never had gait symptoms. Objective. To study the effects of intestinal levodopa/carbidopa infusion in unresponsive-FOG that appears in PD patients treated with subthalamic nucleus deep brain stimulation. Methods. We retrospectively collected and analyzed demographic, clinical, and therapeutic data from five PD patients treated with subthalamic nucleus stimulation who developed unresponsive-FOG and received intestinal levodopa/carbidopa infusion as an alternative therapy. FOG was measured based on scores in item 14 of the Unified Parkinson’s Disease Rating Scale before and after intestinal levodopa infusion. Results. Administration of intestinal levodopa caused improvement of FOG in the “ON” state in four patients (80%) by 2 or more points in item 14 of the Unified Parkinson’s Disease Rating Scale. The improvement was maintained for at least 12 months. Conclusions. Intestinal levodopa infusion may be a valuable therapeutic option for unresponsive-FOG developed after subthalamic nucleus deep brain stimulation.
Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar ...dysfunction (MSA-C).
To identify novel disease mechanisms we performed a blood transcriptomic study investigating differential gene expression changes and biological process alterations in MSA and its clinical subtypes.
We compared the transcriptome from rigorously gender and age-balanced groups of 10 probable MSA-P, 10 probable MSA-C cases, 10 controls from the Catalan MSA Registry (CMSAR), and 10 Parkinson Disease (PD) patients.
Gene set enrichment analyses showed prominent positive enrichment in processes related to immunity and inflammation in all groups, and a negative enrichment in cell differentiation and development of the nervous system in both MSA-P and PD, in contrast to protein translation and processing in MSA-C. Gene set enrichment analysis using expression patterns in different brain regions as a reference also showed distinct results between the different synucleinopathies.
In line with the two major phenotypes described in the clinic, our data suggest that gene expression and biological processes might be differentially affected in MSA-P and MSA-C. Future studies using larger sample sizes are warranted to confirm these results.
Multiple system atrophy (MSA) is a highly debilitating, rare neurodegenerative disorder with two clinical motor variants (parkinsonian or MSA-P and cerebellar or MSA-C). There is a wide span of motor ...and non-motor symptoms (NMS) that progress over time. We studied the cohort from the Catalan Multiple System Atrophy Registry (CMSAR) to determine which symptoms are most likely to progress throughout a 2-year follow-up.
We analyzed baseline, 12-month, and 24-month follow-up evaluations from the 80 cases recruited by the CMSAR. Evaluations included the UMSARS assessment, cognitive and neuropsychiatric evaluations, and a non-motor scale (NMSS-PD). Statistical analysis was done using a Generalized Estimated Equations (GEE) model.
Both UMSARS I and II sub-scores significantly increased at 12- and 24-month follow-ups (p < 0.001), with a median total score increase of 11 and 12.5 points, respectively. Items on UMSARS I that significantly worsened were mostly motor affecting daily activities. NMS, including urinary and sexual dysfunction, as well as sleep difficulties showed a significant progression on the NMSS-PD; however, other NMS such as postural hypotension, gastrointestinal, and mood dysfunction, although prevalent, did not show a clear progression on clinical scales.
Within 24 months and as early as 12 months, MSA cases may experience significant motor worsening, affecting basic daily activities. NMS are prevalent; however, not all clinical scales register a clear progression of symptoms, perhaps suggesting that they are not sensitive enough for non-motor evaluation.
Neuroinflammation is a potential player in neurodegenerative conditions, particularly the aggressive ones, such as multiple system atrophy (MSA). Previous reports on cytokine levels in MSA using ...serum or cerebrospinal fluid (CSF) have been inconsistent, including small samples and a limited number of cytokines, often without comparison to Parkinson's disease (PD), a main MSA differential diagnosis.
Cross-sectional study of CSF levels of 38 cytokines using a multiplex assay in 73 participants: 39 MSA patients (19 with parkinsonian type MSAp, 20 with cerebellar type MSAc; 31 probable, 8 possible), 19 PD patients and 15 neurologically unimpaired controls. None of the participants was under non-steroidal anti-inflammatory drugs at the time of the lumbar puncture.
There were not significant differences in sex and age among participants. In global non-parametric comparisons FDR-corrected for multiple comparisons, CSF levels of 5 cytokines (FGF-2, IL-10, MCP-3, IL-12p40, MDC) differed among the three groups. In pair-wise FDR-corrected non-parametric comparisons 12 cytokines (FGF-2, eotaxin, fractalkine, IFN-α2, IL-10, MCP-3, IL-12p40, MDC, IL-17, IL-7, MIP-1β, TNF-α) were significantly higher in MSA vs. non-MSA cases (PD + controls pooled together). Of these, MCP-3 and MDC were the most significant ones, also differed in MSA vs. PD, and were significant MSA-predictors in binary logistic regression models and ROC curves adjusted for age. CSF levels of fractalkine and MIP-1α showed a strong and significant positive correlation with UMSARS-2 scores.
Increased CSF levels of cytokines such as MCP-3, MDC, fractalkine and MIP-1α deserve consideration as potential diagnostic or severity biomarkers of MSA.
•CSF levels of 12 cytokines were higher in MSA (n = 39) vs. PD + controls (n = 19 & 15).•Younger age and increasing CSF levels of MCP-3 and MDC were MSA predictors in adjusted models.•CSF levels of fractalkine and MIP-1α correlated with UMSARS-2 scores.•CSF levels of these cytokines might be diagnostic or severity MSA biomarkers.
Spasticity is a medical problem with a high incidence that significantly impact on the quality of life of patients and their families.
To analyze and to answer different questions about the use of ...botulinum toxin type A (BTA) in our clinical practice.
A group of experts in neurology develop a list of topics related with the use of BTA. Two big groups were considered: spasticity in adults and in children with cerebral palsy. A literature search at PubMed for English, French, and Spanish language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow for modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of spasticity in adults, such as methods for evaluating spasticity, infiltration techniques, doses, number of infiltration points, etc. Regarding spasticity in children with cerebral palsy, the document included questions about minimum age of infiltration, methods of analgesia, etc.
This review is a tool for continuous training for neurologist and rehabilitation specialist and residents of both specialties, about different specific areas of the management of BTA.
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